Adoptive cellular therapy (ACT) has dramatically changed the landscape of immunotherapy; however, only a small proportion of solid tumor patients have benefited from these advances due to i) heterogeneity of tumor antigen expression, ii) tumor escape (e.g., only one target is addressed), or iii) off-target toxicities (e.g., expression of targets on normal tissues). ACTolog® concept, utilizing antigen specific T-cells (IMA101), identified by the Immatics’ proprietary XPRESIDENT® technology, is intended to overcome these limitations by introducing multiple novel tumor targets. ACTolog® is a personalized ACT approach in which autologous T-cell products are manufactured against the most relevant tumor target peptides for individual patients whose tumors are positive against a predefined target warehouse. Target positive tumors are identified by qPCR. Expression levels predictive for antigen presentation are determined by mass spectrometry. Autologous T-cells against ACTolog targets are in vitro primed in the presence of IL-21 followed by HLA tetramer-guided cell sorting and expansion prior to infusion. IMA101-101 is a first-in-human clinical trial in HLA-A*02:01 positive patients with relapsed or refractory solid tumors using the multitargeted ACTolog® approach in which up to four products with different tumor target-specificities are manufactured and infused for each patient. We developed two flow cytometric phenotyping assays that allow us to determine the frequency of target-specific cells in the final product and persisting cells in the blood as well as to deeply characterize the memory marker expression (CD45RA, CCR7, CD27, CD28, CD45RO, CD62L, CD57, CD127) and immune checkpoint expression (CD137, LAG-3, PD-1, TIGIT, TIM-3) of target-specific cells. Product characterization and initial persistence data of the three first treated patients revealed a high prevalence of persisting target-specific cells in the blood until 2 months after infusion as well as a favorable phenotype of target-specific cells. At the conference 6 months’ data for one patient will be available and presented.
Citation Format: Regina Mendrzyk, Alexander Ulges, Thorsten Demberg, Geoffrey Stephens, Carsten Reinhardt, Steffen Walter, Dominik Maurer. Cellular immunomonitoring for personalized adoptive cellular therapy trial ACTolog® (IMA101-101) [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A015.